Longitudinal Study Of Cognitive Aging Research Articles

The Common Marmoset as a Translational Model for Longitudinal Studies of Cognitive Aging and Individual Vulnerability to Decline.

In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.

The memory binding test in a longitudinal study of cognitive aging and preclinical disease.

The Memory Binding Test (MBT) shows promise in detecting early cognitive changes associated with Alzheimer's disease (AD). This study assesses the psychometric properties (i.e., construct and criterion validity, test-retest reliability) of the MBT and its sensitivity to incipient disease and incident cognitive impairment. One hundred forty-nine cognitively unimpaired adults ages 45-85 completed the MBT and neuropsychological tests at baseline; 132 returned for 2-year follow-up. Based on neuroradiological ratings of amyloid positron emission tomography and MRI markers at baseline, they were categorized as healthy (n = 94) or having preclinical disease (n = 55, either on the AD continuum or having non-AD pathologic change). Construct validity was assessed by the associations between MBT scores, demographics, and neuropsychological scores within the healthy group. Criterion validity was assessed by testing how MBT scores correlate with AD biomarkers, differ and discriminate between groups at baseline, and predict incident cognitive impairment. MBT scores decreased with age and were strongly associated with memory and global cognition. MBT scores were largely not associated with amyloid, hippocampal volume, or AD signature cortical volume but related to white matter lesion volume in those with preclinical disease. The preclinical groups performed worse on MBT immediate free recall at baseline than the healthy group, but no scores predicted incident cognitive impairment at follow-up. Most scores demonstrated modest test-retest reliability. This study demonstrates that the MBT has adequate construct validity in cognitively unimpaired adults, moderate sensitivity to preclinical disease cross-sectionally, and limited prognostic utility. Careful consideration of demographic influences on score interpretation remains necessary. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for The Memory Binding Test in a Longitudinal Study of Cognitive Aging and Preclinical Disease

Supplemental Material for The Memory Binding Test in a Longitudinal Study of Cognitive Aging and Preclinical Disease

A global approach to the epidemiology of cognitive ageing and dementia: Cohort Studies of Memory in International Consortium (COSMIC)

AbstractCOSMIC (COhort Studies of Memory in International Consortium) is an international consortium of longitudinal studies of cognitive aging and dementia, currently comprising 57 cohorts from 39 countries across 6 continents, comprising 186,000 participants (49% White, 8% Black, 21% Asian, 20% Hispanic, 2% Other). COSMIC embraces the power of collaboration through horizontal partnerships, with pooled and coordinated analyses after rigorous harmonization to examine ethno‐geographic differences in risk/protective factors and biomarkers, harness data from under‐represented populations, and permit cross‐validation in a field notorious for non‐replicable results. Analyses thus far have demonstrated that the cross‐national variation in prevalence of MCI is lower than generally reported, with commonality of most risk factors. The effect sizes of risk factors do, however, vary in populations, with APOE*4 and diabetes being associated with greater rates of decline in Asian than White populations. High school education is a significant threshold for protection against cognitive decline in later life, especially in Black and Asian populations. Physical activity shows a dose‐dependent relationship with incident dementia, suggesting that older adults should do three to six hours of physical activity per week for maximum cognitive benefits. The range and depth of such findings continues to grow, as is the community of researchers in both high and low‐middle income countries. With its global reach, open sharing of data and diverse network of researchers, COSMIC is creating a truly global epidemiology of dementia that is needed to deal with the world‐wide inequity in research, and meet the ambitious goals of the 2017 World Health Assembly to address the global epidemic of dementia and the hopes of people at risk of dementia everywhere.

Self-reported mid- to late-life physical and recreational activities: Associations with late-life cognition.

Physical and recreational activities are behaviors that may modify risk of late-life cognitive decline. We sought to examine the role of retrospectively self-reported midlife (age 40) physical and recreational activity engagement - and self-reported change in these activities from age 40 to initial study visit - in predicting late-life cognition. Data were obtained from 898 participants in a longitudinal study of cognitive aging in demographically and cognitively diverse older adults (Age: range = 49-93 years, M = 75, SD = 7.19). Self-reported physical and recreational activity participation at age 40 and at the initial study visit were quantified using the Life Experiences Assessment Form. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 2-17 years) using the Spanish and English Neuropsychological Assessment Scales, which measure verbal episodic memory, semantic memory, visuospatial processing, and executive functioning. Physical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at the initial visit and with global cognitive slope. However, change in physical activities after age 40 was not associated with cognitive outcomes. In contrast, recreational activity engagement - both at age 40 and change after 40 - was predictive of cognitive intercepts and slope. Retrospectively self-reported midlife physical and recreational activity engagement were strongly associated with late-life cognition - both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading) after age 40 is more strongly associated with late-life cognition than continued maintenance of physical activity levels.

Mid‐ to late‐life physical and recreational activities: Associations with late‐life cognition

AbstractBackgroundPhysical and cognitively stimulating recreational activities are lifestyle factors that may modify risk of late‐life cognitive decline. We sought to examine the role of retrospective ratings of mid‐life (age 40) physical and recreational activity engagement – and change in these activities from age 40 to study entry – in predicting late‐life cognition. We hypothesized that higher self‐reported levels of physical and recreational activities at age 40, and less decline in these activities over time, would be associated with higher levels of late‐life cognition and less rapid cognitive decline.MethodData were obtained from 898 participants in the University of California Davis Aging and Diversity Cohort, a longitudinal study of cognitive aging in demographically and cognitively diverse older adults. Participants ranged in age from 49‐93 years (M = 75, SD = 7.19). Self‐reported physical and recreational activity participation at age 40 and at study entry were quantified using the Life Experiences Assessment Form. Confirmatory factor analysis established the unidimensionality and longitudinal measurement invariance of physical and recreational activity levels at age 40 and at study entry. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 0‐17 years) using the Spanish and English Neuropsychological Assessment Scales, which measures episodic memory, semantic memory, visuospatial processing, and executive functioning. Multilevel structural equation modeling was used to regress four cognitive intercepts and one global cognitive slope onto age 40 and change factors for physical and recreational activities, in separate models.ResultPhysical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at study entry and with global cognitive slope. However, change in physical activities was not associated with cognitive outcomes. In contrast, recreational activity engagement – both at age 40 and change after age 40 – was predictive of cognitive intercepts and slope.ConclusionMid‐life physical and recreational activity engagement were strongly associated with late‐life cognition – both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading, arts & crafts) after age 40 is more strongly associated with late‐life cognition than continued maintenance of physical activity levels.

Topological relationships between perivascular spaces and progression of white matter hyperintensities: A pilot study in a sample of the Lothian Birth Cohort 1936.

Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesized to also have topological proximity. However, this and the influence of their spatial proximity on WMH progression are unknown. We analyzed longitudinal MRI data from 29 out of 32 participants (mean age at baseline = 71.9 years) in a longitudinal study of cognitive aging, from three waves of data collection at 3-year intervals, alongside semi-automatic segmentation masks for PVS and WMH, to assess relationships. The majority of deep WMH clusters were found adjacent to or enclosing PVS (waves−1: 77%; 2: 76%; 3: 69%), especially in frontal, parietal, and temporal regions. Of the WMH clusters in the deep white matter that increased between waves, most increased around PVS (waves−1–2: 73%; 2–3: 72%). Formal statistical comparisons of severity of each of these two SVD markers yielded no associations between deep WMH progression and PVS proximity. These findings may suggest some deep WMH clusters may form and grow around PVS, possibly reflecting the consequences of impaired interstitial fluid drainage via PVS. The utility of these relationships as predictors of WMH progression remains unclear.

A HABLE study of the relationship of blood‐based biomarkers of AD and cognition functioning in the cognitively normal: The impact of ethnicity

AbstractBackgroundBlood‐based biomarkers of amyloid accumulation (Abeta40, Abeta 42), markers of neurodegeneration (NfL) and markers of neuronal injury (Tau) have all been proposed as biomarkers of early brain changes linked to the development of cognitive impairment and Alzheimer’s disease. The impact of ethnic differences on this relationship has received little attention. The current study examined the relationship of these blood‐based biomarkers to performance on cognitive tests in cognitively normal older Mexican Americans (MA) and Non‐Hispanic Whites (NHW) to assess the impact of ethnicity.MethodCognitively normal participants were drawn from a community‐based, longitudinal study of cognitive aging in MAs. 647 MAs (447 females, 200 males) and 644 NHWs (372 females, 272 males) were administered a neuropsychological battery to assess current level of cognitive functioning. Levels of plasma total tau, Abeta 40, Abeta 42and NfL were assayed via Single Molecule Array (Simoa) technology. Data were analyzed using t tests and linear regression.ResultMAs were significantly younger and had significantly fewer years of education than NHWs. MAs had higher levels of Abeta 40, Abeta 42 and NfL and lower levels of total tau. Regression analyses by ethnicity controlling for age and education revealed no significant relationship between any of the markers and any of the cognitive tests for MAs. Regression analyses for NHWs showed significant relationships between measures of memory, language, processing speed and Abeta 40; executive functions and NfL and attention and tau and Abeta 42.ConclusionThe results of the current research support the importance of assessing ethnic differences in the relationship of these biomarkers to cognitive functioning. It is likely that other biomarkers may be better predictors of cognitive functioning and cognitive decline for MAs. Further investigation of the nature of the relationship of specific biomarkers to specific cognitive functions in cognitively normal NHWs including neuroimaging is warranted.

Sex differences in cognitive aging: a 4-year longitudinal study in marmosets

Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10–12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (∼5 years) to old age (∼9 years). We characterized aging trajectories using reversal learning with different stimuli each year. Marmosets initially improved on cognitive performance due to practice, but worsened in the final year, suggesting the onset of age-related decline. Cognitive impairment emerged earlier in females than males and was more prominent for discrimination than for reversal learning. Sex differences in cognitive aging could not be explained by differences in motivation or motor abilities, which improved or remained stable across aging. Likewise, males and females did not differ in aging trajectories of overall behavior or reactivity to a social stressor, with the exception of a progressive decline in the initiation of social behavior in females. Patterns of cognitive aging were highly variable across marmosets of both sexes, suggesting the potential for pathological aging for some individuals. Future work will link individual cognitive trajectories to neuropathology in order to better understand the relationships between neuropathologic burden and vulnerability to age-related cognitive decline in each sex.

Relation of neuroticism to frontal cortical transcriptome and Alzheimer’s disease

AbstractBackgroundPrior studies have shown that certain personality traits are associated with differences in aging‐related cognitive decline and incidence of Alzheimer’s disease (AD). Neuroticism, proneness to pscyhological distress, worsens cognitive decline while conscientiousness is protective. However, the molecular composition of these personality traits and the series of molecular events that lead from personality traits to AD in the brain is unknown.MethodWe examined data from 1419 participants in one of two longitudinal studies of cognitive aging with prospectively collected brains at autopsy: the Religious Order Study and the Rush Memory & Aging Project (ROSMAP). We accessed RNA sequence data (>13,000 genes) from the dorsolateral prefrontal cortex (DLPFC); linear regression adjusting for age, sex, and education. We performed a mediation analysis to assess whether certain modules mediate the association of neuroticism to cognitive decline.ResultWe first confirmed that neuroticism contributes to accelerated cognitive decline and AD onset (p=6.75x10‐7) while conscientiousnessis protective (p=4.34x10‐4). We then evaluated the 6 gene modules previously associated with cognitive decline (p<0.001) and found that three of them displayed some association with neuroticism (p<0.05). Mediation modeling suggests that these three modules of co‐expressed genes are altered by in individual’s with greater neuroticism. Neurotic is associated with higher m7 which in turn is related to cognitive decline (p=0.008) than its direct causal effect on cognitive decline which is not mediated through m7 (p=0.042).ConclusionWe demonstrate neuroticism is associated widespread differences in RNA profiles and that these differences contribute to the onset of AD. Although results need further investigation, they identify a new gene signature that could be used to develop new therapies that minimize the risk of AD in individuals with a neurotic personality.

Cardiovascular Risk Factors, Cognitive Dysfunction, and Mild Cognitive Impairment

Objectives: The present study sought to evaluate the contribution of cardiovascular risk factors to cognitive functioning in a sample of Mexican Americans diagnosed with mild cognitive impairment (MCI). Methods: Hypertension, diabetes, dyslipidemia, and obesity were diagnosed based on self-report and/or standardized procedures. Cognitive function was measured with MMSE, Logical Memory I and II, Trail A & B, FAS, animal naming, and digit span tests. Independent samples t tests and two-way ANOVAs were conducted for analyses, adjusting for relevant covariates. We studied 100 Mexican Americans (65 female) with MCI, ages 50–86, from a longitudinal study of cognitive aging conducted at the University of North Texas Health Science Center. Results: A difference between subjects with and without obesity and memory scores was shown by t tests. Two-way ANOVAs detected an association between the coexistence of hypertension and diabetes with language measures, diabetes and dyslipidemia with executive function, and diabetes and obesity with memory and language measures. Conclusions: This study provides additional evidence about the link between cardiovascular risk factors and cognitive dysfunction in MCI subjects, and also demonstrated that comorbid risk factors increased the degree of cognitive deficit in many areas, which may indicate a higher risk of developing dementia.

Association of Hospitalization with Long-Term Cognitive Trajectories in Older Adults.

Hospitalizations are associated with cognitive decline in older adults. To determine the association between hospitalization characteristics and the trajectory of cognitive function in older adults. Population-based longitudinal study of cognitive aging. Olmsted Medical Center and Mayo Clinic, the only centers in Olmsted County, Minnesota, with hospitalization capacity. Individuals without dementia at baseline, with consecutive cognitive assessments from 2004 through 2017, and at least one visit after the age of 60. The primary outcome was longitudinal changes in global cognitive z-score. Secondary outcomes were changes in four cognitive domains: memory, attention/executive function, language, and visuospatial skills. Hospitalization characteristics analyzed included elective versus nonelective, medical versus surgical, critical care versus no critical care admission, and long versus short duration admissions. Of 4,587 participants, 1,622 had 1 and more hospital admission. Before hospitalization, the average slope of the global z-score was -0.031 units/year. After hospitalization, the rate of annual global z-score accelerated by -0.051 (95% CI = -0.057, -0.045) units, P < .001, resulting in an estimated annual slope after the first hospitalization of -0.082. The accelerated decline was found in all four cognitive domains (memory, visuospatial, language, and executive, all P < .001). The acceleration of the decline in global z-score following hospitalization was greater for medical compared to surgical hospitalizations (slope change following hospitalization = -0.064 vs -0.034 for medical vs surgical, P < .001), and nonelective compared to elective admissions (slope change following hospitalization = -0.075 vs -0.037 for nonelective vs elective, P < .001). The acceleration of cognitive decline was not different for hospitalization with intensive care unit admission versus not. Hospitalization of older adults is associated with accelerated decline of global and domain-specific cognitive domains, with the rate of decline dependent upon type of admission. The clinical impact of this accelerated decline will depend on the individual's baseline cognitive reserve and expected longevity.

Association of Apolipoprotein E ɛ4, Educational Level, and Sex With Tau Deposition and Tau-Mediated Metabolic Dysfunction in Older Adults

While amyloidosis is an early event in the Alzheimer disease (AD) biomarker cascade, a complex interplay among the apolipoprotein E (APOE) ɛ4 allele, educational levels, and sex may be associated with an individual's resilience to dementia. To assess whether APOE ɛ4, educational levels, and sex are associated with regional tau deposition and tau-mediated metabolic dysfunction in older adults. Population-based cohort study of individuals aged 65 years and older enrolled between January 1, 2004, and May 1, 2018, in the Mayo Clinic Study of Aging, a prospective longitudinal study of cognitive aging in Olmsted County, Minnesota. The primary outcomes were cross-sectional tau burden and the fluorodeoxyglucose (FDG) to tau ratio (as a measure of tau-mediated metabolic dysfunction) assessed by positron emission tomography for 43 atlas-defined regions, with specific focus on the entorhinal, inferior temporal, and posterior cingulate cortices. Using linear regression, APOE ɛ4 status and years of education were the primary exposure variables, with sex additionally investigated through interaction models. The sample included 325 individuals (173 [53%] male; mean [SD] age, 76.1 [7.2] years; 291 [90%] cognitively unimpaired). Although APOE ɛ4 was nominally associated with higher tau deposition (β = 0.05 [95% CI, 0.02-0.09]; P = .001; Cohen d = 0.40) and lower FDG to tau ratio (β = -0.05 [95% CI, -0.08 to -0.01]; P = .008; Cohen d = 0.33) in the entorhinal cortex, these associations were completely attenuated after controlling for global amyloid burden. Education was not associated with regional tau burden or FDG to tau ratio. In the 3 regions of interest, global amyloid burden accounted for the largest proportion of variance in tau deposition among the candidate variables assessed. In the entorhinal cortex, significant interactions were identified between APOE ɛ4 and global amyloid burden on tau (β = 0.25; SE = 0.06; P < .001) and between sex and tau burden on FDG metabolism (β = 0.10; SE = 0.05; P = .049). These results suggest that (1) tau deposition is most significantly associated with amyloidosis; (2) in the presence of abundant amyloidosis, APOE ɛ4 may be associated with accelerated entorhinal cortex tau deposition; and (3) women may have lower resilience to tau, manifested by a higher degree of metabolic dysfunction in the entorhinal cortex in response to tau pathology.

Education and Cognitive Decline: An Integrative Analysis of Global Longitudinal Studies of Cognitive Aging.

The objective of this study was to examine the association between education and incidence of accelerated cognitive decline. Secondary analyses of data from the Health and Retirement Study (HRS), a nationally representative prospective cohort study of U.S. residents were conducted (N = 28,417). Cox proportional hazards survival models were layered on longitudinal mixed-effects modeling to jointly examine healthy cognitive aging and incidence of accelerated cognitive decline consistent with patterns seen in preclinical Alzheimer's disease and related dementias (ADRD). Replication analyses were completed on a database including 62,485 additional respondents from HRS sister studies. Life expectancy ratios (LER) and 95% confidence intervals (CIs) were reported. This study replicated research showing that education was positively associated with cognition at baseline. Model fit improved using the survival method compared to random-slopes models alone. Analyses of HRS data revealed that higher education was associated with delayed onset of accelerated cognitive decline (LER = 1.031 95% CI = [1.013-1.015], p < 1E-06). Replication analyses using data from 14 countries identified similar results. These results are consistent with cognitive reserve theory, suggesting that education reduces risk of ADRD-pattern cognitive decline. Follow-up work should seek to differentiate specific dementia types involved and consider potential mechanisms.

One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle-age; and (3) that males may experience greater age-related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.

Statins and Brain Health: Alzheimer's Disease and Cerebrovascular Disease Biomarkers in Older Adults.

Statins have been proposed to reduce the risk of Alzheimer's disease (AD). Assess whether long-term statin use was associated with neuroimaging biomarkers of aging and dementia. Methods: We analyzed neuroimaging biomarkers in 1,160 individuals aged 65+ from the Mayo Clinic Study of Aging, a population-based prospective longitudinal study of cognitive aging. Statin-treated (5+ years of therapy) individuals had greater burden of mid-and late-life cardiovascular disease (p < 0.001) than statin-untreated (≤3 months) individuals. Lower fractional anisotropy in the genu of the corpus callosum, an early marker of cerebrovascular disease, was associated with long-term statin exposure (p < 0.035). No significant associations were identified between long-term statin exposure and cerebral amyloid or tau burden, AD pattern neurodegeneration, or white matter hyperintensity burden. Long-term statin therapy was not associated with differences in AD biomarkers. Individuals with long-term statin exposure had worse white matter integrity in the genu of the corpus callosum, consistent with the coexistence of higher cerebrovascular risk factor burden in this group.

SUBJECTIVE COGNITIVE IMPAIRMENT AND THE BROAD AUTISM PHENOTYPE

Roughly 4% of the general population embodies personality, language, and other cognitive traits that characterize a subclinical “broad autism phenotype” (BAP) which qualitatively resembles, but is milder than autism spectrum disorder. Among the normal aging population, individuals with subjective cognitive impairment (SCI) have a high prevalence of psychological distress leading us to predict that BAP would be associated with increasing SCI in the context of otherwise normal aging. The Autism Spectrum Quotient questionnaire (AQ) is a self-administered 50 item questionnaire whose questions are categorized into five domains comprised of 10 questions each: social skills, attention switching, attention to detail, communication, and ideas. Answers are dichotomized as either agree or disagree. Each item is scored as a “1” if the individual endorses the autistic trait so that scores can range from 0-50. Scores of 23 and above are the threshold for BAP. The AQ was completed by 419 consecutive members of the Arizona APOE Cohort, a longitudinal study of cognitive aging in which participants undergo detailed neuropsychological testing every two years. SCI was assessed with self and informant versions of the Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS). The MANS and auditory verbal learning test (AVLT) scores were standardized in the longitudinal analysis. 45 individuals scored 23 or above and are categorized as AQ+. The remaining 374 are AQ-. The AQ+ group had disproportionately more men (p=.0005) and a higher proportion of multiple divorces (p=.01), but no differences in age, education, parental status, occupational status, or income category. All comparisons were corrected for sex. At entry, both MANS-self (p<.0001) and MANS-informant (p<.0001) scores were higher in the AQ+ group despite normal neuropsychological scores. Longitudinally, after age 60, the AQ+ group had a greater annual rate of increase in MANS-self (but not informant) scores (0.05 vs 0.02; diff = 0.03; 95%CI: 0.004, 0.05; p=0.02) yet both groups showed only similar mild decline on the AVLT after age 60 (annual change -0.02 vs -0.02; diff = 0.01; 95%CI: -0.01, 0.03; p=0.43) (figure).

Intraindividual reaction time variability predicts prospective memory failures in older adults

ABSTRACTThis study investigated the relationship between intraindividual variability (IIV) in reaction time and prospective memory errors in older adults using data from the Zurich Longitudinal Study of Cognitive Aging (n = 336 individuals aged 66–81 years). The results indicated that increased IIV measured from independent tasks was associated with a greater proportion of prospective memory errors. These significant findings were not influenced by age and did not vary according to prospective memory cue type. Variability is thought to reflect fluctuations in attentional and executive control and these attentional processes may also impact on prospective memory through failure to detect the target cue. The findings suggest, therefore, that measures of variability may have some potential in the identification of older persons who are more vulnerable to everyday errors such as prospective memory failures.

Lifecourse Activity Participation From Early, Mid, and Later Adulthood as Determinants of Cognitive Aging: The Lothian Birth Cohort 1921.

Objectives:To examine potential sensitive periods for activity participation across adulthood to reduce cognitive decline and to determine whether associations persist after accounting for the lifetime stability of cognitive ability.Method:The Lothian Birth Cohort 1921 is a longitudinal study of cognitive aging. Participants were born in 1921 and most completed a mental ability test at the age of 11 years. Cognitive assessments were completed at mean ages 79 (N = 550), 83 (N = 321), 87 (N = 235), and 90 years (N = 129). Participants provided retrospective details of their activity participation for young (20–35 years), mid (40–55 years), and later adulthood (60–75 years), and contemporaneously at age 79.Results:Associations between activity and the level of, and change in, cognitive ability in old age were examined with latent growth curve models. Accounting for demographics and childhood cognitive ability, engagement in leisure activities in midlife was positively associated with cognitive ability level (path coefficient = .32), whereas higher physical activity in later adulthood was associated with less cognitive decline (.27).Discussion:The findings support a lifecourse approach in identifying determinants of cognitive aging; leisure and physical activity during different periods of adulthood may enhance cognitive abilities or reduce decline.

Predictors of Retest Effects in a Longitudinal Study of Cognitive Aging in a Diverse Community-Based Sample.

Better performance due to repeated testing can bias long-term trajectories of cognitive aging and correlates of change. We examined whether retest effects differ as a function of individual differences pertinent to cognitive aging: race/ethnicity, age, sex, language, years of education, literacy, and dementia risk factors including apolipoprotein E ε4 status, baseline cognitive performance, and cardiovascular risk. We used data from the Washington Heights-Inwood Columbia Aging Project, a community-based cohort of older adults (n=4073). We modeled cognitive change and retest effects in summary factors for general cognitive performance, memory, executive functioning, and language using multilevel models. Retest effects were parameterized in two ways, as improvement between the first and subsequent testings, and as the square root of the number of prior testings. We evaluated whether the retest effect differed by individual characteristics. The mean retest effect for general cognitive performance was 0.60 standard deviations (95% confidence interval [0.46, 0.74]), and was similar for memory, executive functioning, and language. Retest effects were greater for participants in the lowest quartile of cognitive performance (many of whom met criteria for dementia based on a study algorithm), consistent with regression to the mean. Retest did not differ by other characteristics. Retest effects are large in this community-based sample, but do not vary by demographic or dementia-related characteristics. Differential retest effects may not limit the generalizability of inferences across different groups in longitudinal research.